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PXD019430

PXD019430 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleVAV3 in ERBB4-mediated cancer cell migration
DescriptionERBB4 is a member of the epidermal growth factor receptor (EGFR)/ERBB subfamily of receptor tyrosine kinases that regulates cellular processes including proliferation, migration and survival. ERBB4 signaling is involved in embryogenesis and homeostasis of adult tissues, but also in human pathologies such as cancer, neurological disorders and cardiovascular diseases. A mass spectrometry screen revealed guanine nucleotide exchange factor (GEF) VAV3, an activator of Rho family GTPases, as a novel ERBB4-interacting protein in breast cancer cells. The ERBB4-VAV3-interaction was confirmed by targeted mass-spectrometry, coimmunoprecipitation experiments, and further defined by demonstrating that kinase activity and tyrosine residues 1022 and 1162 of ERBB4, as well as the intact phosphotyrosine-interacting SH2 domain of VAV3 were necessary for the interaction. ERBB4 was also shown to stimulate tyrosine phosphorylation of the VAV3 activation domain, which is required for GEF activity of VAV proteins. In addition to VAV3, also the other members of the VAV family, VAV1 and VAV2 were shown to coprecipitate with ERBB4. Analyses of the effects of overexpression of dominant-negative VAV3 constructs or downregulation of VAV3 expression by shRNAs in breast cancer cells demonstrated that active VAV3 was involved in ERBB4-stimulated migration. These findings define the VAV GTPases as novel effectors of ERBB4 activity in a signaling pathway relevant for cancer cell migration.
HostingRepositoryPRIDE
AnnounceDate2024-10-22
AnnouncementXMLSubmission_2024-10-22_05:07:41.873.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterJohannes Merilahti
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListiodoacetamide derivatized residue
InstrumentOrbitrap Fusion Lumos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02020-05-27 17:21:29ID requested
12020-06-23 22:15:02announced
22024-10-22 05:07:42announced2024-10-22: Updated project metadata.
Publication List
10.1074/jbc.ra119.010925;
Ojala VK, Knittle AM, Kirjalainen P, Merilahti JAM, Kortesoja M, Tvorogov D, Vaparanta K, Lin S, Kast J, Pulliainen AT, Kurppa KJ, Elenius K, The guanine nucleotide exchange factor VAV3 participates in ERBB4-mediated cancer cell migration. J Biol Chem, 295(33):11559-11571(2020) [pubmed]
Keyword List
submitter keyword: VAV3, Targeted analysis, PRM,ERBB4
Contact List
Klaus Elenius
contact affiliationInstitute of Biomedicine, and Medicity Research Laboratories, University of Turku, Turku, Finland; Turku Bioscience Centre, University of Turku, and Åbo Akademi University, Turku, Finland
contact emailklaus.elenius@utu.fi
lab head
Johannes Merilahti
contact affiliationTurku Bioscience University of Turku
contact emailjohannes.merilahti@utu.fi
dataset submitter
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Dataset FTP location
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PRIDE project URI
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